Some individuals do not become drug abusers despite exposure to and experimentation with drugs of abuse. In contrast, other individuals seem particularly prone to abusing drugs even when the circumstances surrounding exposure appear comparable to that of the non-abuser. There is growing interest in determining factors responsible for this increased individual vulnerability as a means for developing more effective prevention strategies. One factor that might contribute to susceptibility is that certain individuals experience different effects when initially exposed to a drug that increases the probability of continued use. Repeated exposure to the pharmacological properties of the drug might then exacerbate its use by other mechanisms such as the development of physical dependence. The goal of the present proposal is to determine whether certain behavioral variables, namely prevailing behavioral conditions and behavioral experience, can produce different drug effects in humans. More specifically, the effects of amphetamine on punished (point substraction) responding will be assessed before and after experience responding under an avoidance schedule (avoidance of point loss). Previous animal research has demonstrated that prior to such experience, amphetamine decreases punished responding. However, if avoidance responding is maintained either concurrently or if the animal has had a history of responding under an avoidance contingency, the effects of amphetamine are drastically altered and increases in punished responding are observed. Alterations in the effects of other drugs as a function of behavioral experience have also been found but the influence of behavioral experience appears limited to drugs of abuse. Thus, in the present experiments, the ability of behavioral experience to modify effects of mazindol, a drug which has similar behavioral properties to amphetamine but is not abused, will also be determined. If successful, this research will open the way for behavioral research in humans to determine whether other behavioral effects more directly relevant to drug abuse (e.g., discriminative stimulus and reinforcing effects) can also be altered by behavioral experience. In addition, the demonstration that animal studies can be replicated in humans gives confidence that future animal studies in this area will be relevant to humans.